What is GBM?
Glioblastoma multiforme (GBM) is the most lethal primary brain tumor in adults. It is characterized by treatment resistance, high recurrence rate, and low survival: median survival rates have remained largely unchanged for 30 years, with a 5-year survival rate of less than 5% (Stupp et al., 2005).
This may be attributed to the cancer’s infiltrative nature into the brain parenchyma and transcriptionally-distinct cellular states, most commonly recognized as: the astro-cyte (AC)-like, mesenchymal (MES)-like, oligodendrocyte progenitor cell (OPC)-like, and neural pro-genitor cell (NPC)-like states (Neftel et al., 2019).
Modeling GBM
Our most recent initiative is the creation of cerebral organoids to use these “in vitro human brains” as 3-D platforms for growing and studying how primary patient-derived glioblastoma tumor stem cells proliferate, invade, migrate and destroy human brain tissue. We have developed a novel model system (GLICO) whereby we retro-engineer patient-derived primary brain tumors (gliomas) into iPSC/hESC-derived human cerebral organoids, ultimately forming tumors that closely phenocopy patient glioblastomas.
Evidence generated by our laboratory and others has shown that patient-derived glioma stem cells (GSCs) are the most biologically and phenotypically relevant cells to the parental tumor in patients. Using hESC-derived cerebral organoids and patient-derived GSCs, we demonstrate a powerful tool for modeling human GBM within a primitive, human brain microenvironment.
